Upregulation of miR‑122 is associated with cardiomyocyte apoptosis in atrial fibrillation

  • Authors:
    • Xiangqun Zhang
    • Wenli Jing
  • View Affiliations

  • Published online on: June 4, 2018     https://doi.org/10.3892/mmr.2018.9124
  • Pages: 1745-1751
Metrics: HTML 0 views | PDF 0 views     Cited By (CrossRef): 0 citations

Abstract

Atrial fibrillation (AF) is a common cardiac arrhythmia, which is associated with increased cardiovascular morbidity and mortality. microRNA (miRNA/miR)‑122 has been reported to be related with heart diseases, however, the functional role of miR‑122 in atrial fibrillation is unclear. Therefore, the aim of the present study was to investigate the roles of miR‑122 in atrial fibrillation. Male C57BL/6 mice were divided into the following three groups: Control, sham‑operation and AF. Mice in the AF group received transesophageal rapid atrial stimulation for the induction of AF. Cardiomyocytes isolated from mice in the AF group and were transfected with miR‑122 inhibitors. Reverse transcription‑quantitative polymerase chain reaction was used to assess the expression of miR‑122 in cardiomyocytes isolated from mice in the AF, sham‑operation and control groups, and in cells transfected with miR‑122 inhibitors. MTT and TUNEL assays were used to evaluate cardiomyocyte viability and apoptosis, respectively. Western blot analysis was used to assess the expression levels of extracellular signal‑regulated kinase (ERK) and phosphorylated (p)‑ERK, as well as the apoptosis‑associated proteins caspase‑3 and B‑cell lymphoma 2‑like 1 (Bcl‑x). The present results demonstrated that miR‑122 expression in the AF group was significantly increased compared with the sham‑operation and control groups, whereas it was significantly decreased following transfection with the miR‑122 inhibitor. Cardiomyocyte viability was increased and their apoptosis rate was significantly decreased following miR‑122 transfection. In addition, the expression of the anti‑apoptotic protein Bcl‑x was significantly upregulated, whereas the expression of the pro‑apoptotic caspase‑3 was significantly downregulated following miR‑122 inhibition. Furthermore, the p‑ERK/total ERK ratio was significantly increased in the miR‑122 inhibitor group compared with the AF and control groups. The present results suggested that miR‑122 may be implicated in the molecular mechanisms underlying the proliferation and apoptosis of cardiomyocytes in AF.

References

1 

Krogh-Madsen T, Abbott GW and Christini DJ: Effects of electrical and structural remodeling on atrial fibrillation maintenance: A simulation study. PLoS Comput Biol. 8:e10023902012. View Article : Google Scholar : PubMed/NCBI

2 

Xiao J, Liang D, Zhao H, Liu Y, Zhang H, Lu X, Liu Y, Li J, Peng L and Chen YH: 2-Aminoethoxydiphenyl borate, a inositol 1,4,5-triphosphate receptor inhibitor, prevents atrial fibrillation. Exp Biol Med (Maywood). 235:862–868. 2010. View Article : Google Scholar : PubMed/NCBI

3 

Zoni-Berisso M, Lercari F, Carazza T and Domenicucci S: Epidemiology of atrial fibrillation: European perspective. Clin Epidemiol. 6:213–220. 2014. View Article : Google Scholar : PubMed/NCBI

4 

Gaita F, Corsinovi L, Anselmino M, Raimondo C, Pianelli M, Toso E, Bergamasco L, Boffano C, Valentini MC, Cesarani F and Scaglione M: Prevalence of silent cerebral ischemia in paroxysmal and persistent atrial fibrillation and correlation with cognitive function. J Am Coll Cardiol. 62:1990–1997. 2013. View Article : Google Scholar : PubMed/NCBI

5 

Wolf PA, Abbott RD and Kannel WB: Atrial fibrillation as an independent risk factor for stroke: The framingham study. Stroke. 22:983–988. 1991. View Article : Google Scholar : PubMed/NCBI

6 

Jones DG, Haldar SK, Hussain W, Sharma R, Francis DP, Rahman-Haley SL, McDonagh TA, Underwood SR, Markides V and Wong T: A randomized trial to assess catheter ablation versus rate control in the management of persistent atrial fibrillation in heart failure. J Am Coll Cardiol. 61:1894–1903. 2013. View Article : Google Scholar : PubMed/NCBI

7 

Benjamin EJ, Wolf PA, D'Agostino RB, Silbershatz H, Kannel WB and Levy D: Impact of atrial fibrillation on the risk of death The framingham heart study. Circulation. 98:946–952. 1998. View Article : Google Scholar : PubMed/NCBI

8 

Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. View Article : Google Scholar : PubMed/NCBI

9 

Liu D, Jickling GC, Ander BP, Hull H, Zhan X, Dykstra-Aiello C, Stamova B and Sharp FR: Abstract W P93: MiR-122 improves stroke outcomes after middle cerebral artery occlusion in rats. Stroke. 46:AWP932015.

10 

Esteller M: Non-coding RNAs in human disease. Nat Rev Genet. 12:861–874. 2011. View Article : Google Scholar : PubMed/NCBI

11 

Latronico MV and Condorelli G: MicroRNAs and cardiac pathology. Nat Rev Cardiol. 6:418–429. 2009. View Article : Google Scholar

12 

Lu Y, Zhang Y, Wang N, Pan Z, Gao X, Zhang F, Zhang Y, Shan H, Luo X, Bai Y, et al: MicroRNA-328 contributes to adverse electrical remodeling in atrial fibrillation. Circulation. 122:2378–2387. 2010. View Article : Google Scholar : PubMed/NCBI

13 

Girmatsion Z, Biliczki P, Bonauer A, Wimmer-Greinecker G, Scherer M, Moritz A, Bukowska A, Goette A, Nattel S, Hohnloser SH and Ehrlich JR: Changes in microRNA-1 expression and IK1 up-regulation in human atrial fibrillation. Heart Rhythm. 6:1802–1809. 2009. View Article : Google Scholar : PubMed/NCBI

14 

Luo X, Pan Z, Shan H, Xiao J, Sun X, Wang N, Lin H, Xiao L, Maguy A, Qi XY, et al: MicroRNA-26 governs profibrillatory inward-rectifier potassium current changes in atrial fibrillation. J Clin Invest. 123:1939–1951. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Li X, Yang Y, Wang L, Qiao S, Lu X, Wu Y, Xu B, Li H and Gu D: Plasma miR-122 and miR-3149 potentially novel biomarkers for acute coronary syndrome. PLoS One. 10:e01254302015. View Article : Google Scholar : PubMed/NCBI

16 

Beaumont J, López B, Hermida N, Schroen B, San José G, Heymans S, Valencia F, Gómez-Doblas JJ, De Teresa E, Díez J and González A: microRNA-122 down-regulation may play a role in severe myocardial fibrosis in human aortic stenosis through TGF-β1 up-regulation. Clin Sci (Lond). 126:497–506. 2014. View Article : Google Scholar : PubMed/NCBI

17 

Schrickel JW, Bielik H, Yang A, Schimpf R, Shlevkov N, Burkhardt D, Meyer R, Grohé C, Fink K, Tiemann K, et al: Induction of atrial fibrillation in mice by rapid transesophageal atrial pacing. Basic Res Cardiol. 97:452–460. 2002. View Article : Google Scholar : PubMed/NCBI

18 

Verheule S, Sato T, Everett T IV, Engle SK, Otten D, Rubart-von der Lohe M, Nakajima HO, Nakajima H, Field LJ and Olgin JE: Increased vulnerability to atrial fibrillation in transgenic mice with selective atrial fibrosis caused by overexpression of TGF-beta1. Circ Res. 94:1458–1465. 2004. View Article : Google Scholar : PubMed/NCBI

19 

Haugan K, Lam HR, Knudsen CB and Petersen JS: Atrial fibrillation in rats induced by rapid transesophageal atrial pacing during brief episodes of asphyxia: A new in vivo model. J Cardiovasc Pharmacol. 44:125–135. 2004. View Article : Google Scholar : PubMed/NCBI

20 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

21 

European Heart Rhythm Association; Heart Rhythm Society, . Fuster V, Rydén LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA, Halperin JL, Le Heuzey JY, et al: ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation-executive summary: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation). J Am Coll Cardiol. 48:854–906. 2006. View Article : Google Scholar : PubMed/NCBI

22 

Chang J, Nicolas E, Marks D, Sander C, Lerro A, Buendia MA, Xu C, Mason WS, Moloshok T, Bort R, et al: miR-122, a mammalian liver-specific microRNA, is processed from hcr mRNA and may downregulate the high affinity cationic amino acid transporter CAT-1. RNA Biol. 1:106–113. 2004. View Article : Google Scholar : PubMed/NCBI

23 

Fernández-Hernando C, Suárez Y, Rayner KJ and Moore KJ: MicroRNAs in lipid metabolism. Curr Opin Lipidol. 22:86–92. 2011. View Article : Google Scholar : PubMed/NCBI

24 

Wei G, He HW, Wang ZM, Zhao H, Lian XQ, Wang YS, Zhu J, Yan JJ, Zhang DG, Yang ZJ and Wang LS: Plasma levels of lipometabolism-related miR-122 and miR-370 are increased in patients with hyperlipidemia and associated with coronary artery disease. Lipids Health Dis. 11–55. 2012.PubMed/NCBI

25 

Corsten MF, Dennert R, Jochems S, Kuznetsova T, Devaux Y, Hofstra L, Wagner DR, Staessen JA, Heymans S and Schroen B: Circulating MicroRNA-208b and MicroRNA-499 reflect myocardial damage in cardiovascular disease. Circ Cardiovasc Genet. 3:499–506. 2010. View Article : Google Scholar : PubMed/NCBI

26 

Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J, Bartel DP, Linsley PS and Johnson JM: Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature. 433:769–773. 2005. View Article : Google Scholar : PubMed/NCBI

27 

Esquela-Kerscher A and Slack FJ: Oncomirs-microRNAs with a role in cancer. Nat Rev Cancer. 6:259–269. 2006. View Article : Google Scholar : PubMed/NCBI

28 

Ma L, Liu J, Shen J, Liu L, Wu J, Li W, Luo J, Chen Q and Qian C: Expression of miR-122 mediated by adenoviral vector induces apoptosis and cell cycle arrest of cancer cells. Cancer Biol Ther. 9:554–561. 2010. View Article : Google Scholar : PubMed/NCBI

29 

Thompson CB: Apoptosis in the pathogenesis and treatment of disease. Science. 267:1456–1462. 1995. View Article : Google Scholar : PubMed/NCBI

30 

Fuchs Y and Steller H: Programmed cell death in animal development and disease. Cell. 147:742–758. 2011. View Article : Google Scholar : PubMed/NCBI

31 

Danial NN and Korsmeyer SJ: Cell death: Critical control points. Cell. 116:205–219. 2004. View Article : Google Scholar : PubMed/NCBI

32 

Galluzzi L, Vitale I, Abrams JM, Alnemri ES, Baehrecke EH, Blagosklonny MV, Dawson TM, Dawson VL, El-Deiry WS, Fulda S, et al: Molecular definitions of cell death subroutines: Recommendations of the nomenclature committee on cell death 2012. Cell Death Differ. 19:107–120. 2012. View Article : Google Scholar : PubMed/NCBI

33 

Ghavami S, Hashemi M, Ande SR, Yeganeh B, Xiao W, Eshraghi M, Bus CJ, Kadkhoda K, Wiechec E, Halayko AJ and Los M: Apoptosis and cancer: Mutations within caspase genes. J Med Genet. 46:497–510. 2009. View Article : Google Scholar : PubMed/NCBI

34 

Youle RJ and Strasser A: The BCL-2 protein family: Opposing activities that mediate cell death. Nat Rev Mol Cell Biol. 9:47–59. 2008. View Article : Google Scholar : PubMed/NCBI

35 

Nagane M, Levitzki A, Gazit A, Cavenee WK and Huang HJ: Drug resistance of human glioblastoma cells conferred by a tumor-specific mutant epidermal growth factor receptor through modulation of Bcl-XL and caspase-3-like proteases. Proc Natl Acad Sci USA. 95:5724–5729. 1998. View Article : Google Scholar : PubMed/NCBI

36 

McCubrey JA, Steelman LS, Chappell WH, Abrams SL, Wong EW, Chang F, Lehmann B, Terrian DM, Milella M, Tafuri A, et al: Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance. Biochim Biophys Acta. 1773:1263–1284. 2007. View Article : Google Scholar : PubMed/NCBI

37 

Cagnol S and Chambard JC: ERK and cell death: Mechanisms of ERK-induced cell death-apoptosis, autophagy and senescence. FEBS J. 277:2–21. 2009. View Article : Google Scholar : PubMed/NCBI

38 

Hu H, Jiang C, Li G and Lü J: PKB/AKT and ERK regulation of caspase-mediated apoptosis by methylseleninic acid in LNCaP prostate cancer cells. Carcinogenesis. 26:1374–1381. 2005. View Article : Google Scholar : PubMed/NCBI

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August 2018
Volume 18 Issue 2

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Copy and paste a formatted citation
APA
Zhang, X., & Zhang, X. (2018). Upregulation of miR‑122 is associated with cardiomyocyte apoptosis in atrial fibrillation. Molecular Medicine Reports, 18, 1745-1751. https://doi.org/10.3892/mmr.2018.9124
MLA
Zhang, X., Jing, W."Upregulation of miR‑122 is associated with cardiomyocyte apoptosis in atrial fibrillation". Molecular Medicine Reports 18.2 (2018): 1745-1751.
Chicago
Zhang, X., Jing, W."Upregulation of miR‑122 is associated with cardiomyocyte apoptosis in atrial fibrillation". Molecular Medicine Reports 18, no. 2 (2018): 1745-1751. https://doi.org/10.3892/mmr.2018.9124